V-ATPases are multimeric proton-pumps responsible for generating an electrochemical gradient across biological membranes. A single eukaryotic cell has several organelles that require a transmembrane potential to function. V-ATPases must be differentially targeted and regulated for each of these organelles. The working hypothesis is that: (1) V-ATPases bound to composition. (2) V-ATPase subunits will fall into two classes; a) subunits that are common to all V-ATPases within the cell and b) subunits unique to a specific V-ATPase in a specific organelle. (3) The class of organelle-specific V-ATPase subunits will be composed of groups of functional isoforms, encoded by gene families, with one isoform per organelle. (4) Organelle-specific subunits will contain information required for targeting or regulating a V-ATPase for a specific organelle.